Determinations of serum tumor necrosis factor alpha in corneal allografts

Corneal allograft rejection culminates in a series of interactions between different classes of antigen presenting cells, cytokines and leukocytes. Tumor necrosis factor-alpha (TNF-alpha) was recently reported to be elevated in acute rejection of solid organ transplants. This cytokine is released early in immune activation and may be detected in the peripheral circulation. Serial determinations of TNF-alpha serum levels were performed following experimental corneal allografts. Lewis rats received 3.5 mm orthotopic corneal grafts of MHC-incompatible Wistar-Furth donors. TNF-alpha concentrations were measured in serum samples collected pre- and postoperatively and measured by micro ELISA. Clinical observations revealed graft rejection in 65.5% of corneal transplants 14 +/- 4 days following grafting. The mean serum level of TNF-alpha in control animals without corneal graft (group I) was 41 +/- 12 pg/ml. Animals following keratoplasty without allograft rejection (group II) showed a mean TNF-alpha level of 54 +/- 16 pg/ml that did not differ from group I. The rejection group III displayed significantly higher TNF-alpha levels (98 +/- 16 pg/ml, p < 0.05). These significantly elevated levels were found even before the diagnosis of rejection was established by clinical criteria. These data suggest systemic immunoreactivity to corneal allografts. Elevated levels of cytokines may provide valuable information in recipients undergoing rejection and may also provide a rationale for systemic immunotherapy in some instances.